Accelerating Drug Discovery in Michigan

BY PETER TOOGOOD, DIRECTOR OF MICHIGAN DRUG DISCOVERY AND RESEARCH & ASSOCIATE PROFESSOR, COLLEGE OF PHARMACY, UNIVERSITY OF MICHIGAN

When University of Michigan (U-M) scientist Isin Cakir, Ph.D. discovered a link between an enzyme called histone deacetylase 6 (HDAC6) and obesity in mice, he knew the next step in his research would be identifying molecules that could potentially block that same enzyme safely in humans.

To pursue that investigation, he turned to Michigan Drug Discovery (MDD), U-M’s university-spanning program, to help coordinate and fund drug discovery projects across campus. By working with MDD, Cakir was able to optimize his compounds, which were recently disclosed in a 2022 patent application, for testing relevant disease models.

The ability to capitalize on fundamental new discoveries in biology, by applying the tools of drug discovery, is at the core of what MDD was established to achieve. Academic research programs are replete with opportunities to translate fundamental studies of human health and disease into new methods of treatment. However, while university faculty are specialists in their fields, they may have less expertise or fewer resources for translating basic science research into new medicines – which is where the MDD plays an important role.

Once associated with a project, MDD is a forcemultiplier that can bring critical experience and resources to early-stage drug discovery projects by connecting faculty with relevant experts on campusincluding scientists who have experience bringing new treatments to the market in the pharmaceutical industry. By providing faculty with funding to conduct important proof-of-concept experiments, along with mentorship and guidance, MDD helps researchers identify and optimize novel drug candidates. The program supports research teams seeking new therapies for a wide range of diseases, including cancer, heart disease, opioid addiction, pain, and bacterial and viral infections.

The staff at MDD select projects to support through a competitive review process that includes input from industry experts. Top projects are teamed with one or more of several research core facilities on campus that specialize in high throughput screens, drug repurposing, medicinal chemistry, structural biology, natural products, or pharmacokinetics. Most projects rely on multiple cores to progress and MDD helps to coordinate resources while providing advice on prioritization and pivotal experiments.

Since its launch in 2012 (as the Center for the Discovery of New Medicines), MDD has invested over $3.5 million in drug discovery research at U-M. These investments have gone on to garner more than $48 million in external grant support, a 14-fold return on investment. In addition, the work supported by MDD has contributed to more than 80 publications and patent applications, and several projects have been licensed or formed the basis of new company formation.

The benefits of working with MDD are not limited to U-M faculty. MDD, and its associated research cores, also work with external partners, including faculty from other universities and researchers at biotech companies. For example, the high throughput screening lab recently completed projects for groups at the Van Andel Institute in Grand Rapids and for a biotech company in San Diego.

Although the considerable investment necessary to advance basic science projects to the clinic, and ultimately to patients, can be daunting, MDD see’s multiple opportunities to germinate and grow these projects in U-M labs. New ways to identify drug targets, better screening technologies, and the application of machine learning models enable smarter decisionmaking at all stages of drug discovery and are expected to trim costs while increasing the probability of success. These developments help set the stage for U-M to make major contributions to the discovery and advancement of new medicines that will address the unmet medical needs of patients around the world.

Success stories

Dr. John Traynor and Dr. Andy Alt are conducting work on modulators of the mu opioid receptor seeking ways to combat the devastating effects of the opioid epidemic. This work has been supported by MDD, and recently,the team was rewarded with an STTR grant in conjunction with the U-M startup company, Eleven. Current funding will support the identification of a lead compound for toxicology studies.

In 2020, investigators from the University of Michigan and Michigan State University were fairly certain that they had identified a new way to treat fibrosis. The researchers had discovered through in vitro experiments that the protein pirin plays a critical role in the onset of fibrosis. They were close to validating pirin as a potential drug target, but they needed to conduct one more critical experiment to convince potential partners of their discovery. With a timely grant from MDD the team was able to secure the final piece of data needed to attract a development partner.

The benefits of working with MDD are not limited to U-M faculty. MDD, and its associated research cores, also work with external partners, including faculty from other universities and researchers at biotech companies.